Methotrexate-induced Changes in Rat Parotid and Submandibular Gland Function

Abstract

Methotrexate (MTX) was injected intraperitoneally at a dose of 15 mg/kg into adult rats daily for three consecutive days. When compared with saline-injected, ad libitum-fed rats or pair-fed saline-injected rats, MTX decreased unstimulated parotid gland weight, RNA content, and amylase content. RNA content was also decreased in submandibular glands. The parotid and submandibular gland outputs of sodium and chloride, but not that of potassium, were decreased following MTX injection. Ductal perfusion demonstrated decreased net efflux of sodium and chloride from the excretory duct of the submandibular gland. The effects of MTX on unstimulated parotid gland weight, RNA content, and amylase content are consistent with its ability to inhibit protein synthesis through depletion of folate co-factors. However, the mechanism by which the alterations in ion transport occurred is not clear at this time.

Effects of chemo-therapeutic drugs used in head and neck cancers on sub-mandibular glands of rats

“…A decrease in total protein and glands' weight as a result of vacuolization and acinus degeneration was an expected result in the methotrexate-treated group of this study. The results of Romaniuk et al [35] and Mc Bride et al [39] studies are also in accordance with our findings. In this case, it is possible to say that the morphological changes are not reflected to the cell function in the methotrexate-treated group.…”

“…In the present study, the decrease in total protein and SMGs weight in the methotrexate-treated group was not statistically significant compared to the control group (p > 0.05). Mc Bride et al [39] and Wolff et al [32] report ed similar results in their study, examining the effects of methotrexate on the total protein concentration of the rats' SMGs. The common point of all these studies is that structural degeneration has not yet been reflected in the function.…”

“…There are studies reported that total protein increases, decreases, or does not change during chemotherapy [31,32,[36][37][38][39][40][41].…”

Digestive System

“…There is shrinking of mucous and serous glands and loss of zymogen granules associated with decreased RNA but unchanged DNA content, attributable to the reduced requirements for protein synthesis. 133,134 As salivary gland function is responsive to adrenergic stimulation, it is not surprising that atrophy occurs following adrenergic blockade. The weights of the submandibular gland in mice were shown to decrease following administration of the β adrenergic blocking agent propranolol.…”

“…13,14 Methotrexate, a folic acid antagonist, has also been reported to cause vacuolization of acinar and ductular cells with reduction of secretory granules in rat salivary glands. 134 Ligation of the main excretory ducts has frequently been used as an experimental model for study of salivary gland atrophy as well as the regeneration that follows removal of the ligature. Following ligature there is atrophy of all cell types but particularly the acinar cells through a process of apoptosis.…”